Chapter 5 - Chemical Messengers

What are 2 types of receptors?

1. Plasma Membrane Receptors

2. Intracellular Receptors

Plasma membrane receptros

span entire length of plasma membrane

Intracellular receptors

located in cytosol of the cell, always interact with DNA in producing a response

4 Features of Ligand-Receptor Interactions

1. Specificity

2. Affinity

3. Saturation

4. Competition

Specificity

ligands bind to a particular & specific protein to initiate a reaction

Affinity

determine the degree at which a ligand binds to a target protein

• receptors with high affinity for a ligand require much less of the ligand to create a response

Saturation

refers to the rate at which receptors receive messeges

Competition

the ability of a molecule to compete with a natural ligand for binding to its receptor

Intercellular Communication

communication that occurs between 2+ cells, cells can be near to each other or far away

Direct intercellular communication

through which cells communicate directly with each other

Indirect intercellular communication

one cell uses a chemical or electrical signal to communicate with another cell. Chemical messengers, hormones, or impulses are often used

Characteristic of Intercellular Communication

1. always involves 2+ cells

2. information is shared by cells and at least 1 responds to it

2 Mechanisms of Intercellular Communication

1. Direct through Gap Junctions

2. Indirect through Chemical Messengers

Direct Communication Through Gap Junctions

Ions moving between adjacent cells through connexons can serve as electrical signals between the cells. In cardiac muscle tissue, movement of ions between neighboring cells signals the cells to contract as a unit

Connexins

Plasma membrane proteins that form gap junctions

Gap Junction

openings between adjacent cells

Connexons

a collection of 6 connexins that bond together and form a channel

Indirect communication though chemical messengers

• cells communicate via ligands that bind reversibly to proteins

• chemical messenger transported through interstitial fluid

What 3 things does the target cell’s response depend on?

1. concentration of the messenger near the target cell

2. number of receptors available to bind the messenger

3. sensitivity of the receptors for the messenger

3 Functional Classifications of Chemical Messengers

1. Paracrines

2. Neurotransmitters

3. Hormones

Paracrines

chemicals that communicate with neighboring cells

• target cell must be close enough that once the paracrine is secreted into the extracellular fluid, it can reach the target cell by simple diffusion

Autocrines

specific group of paracrines; messengers that are released by, and act on the same cell. Regulate their own secretions

3 Types of paracrines

1. Growth Factors

2. Clotting Factors

3. Cytokines

Growth Factors

proteins that stimulate cell growth and development

• ex: nervous system growth factors which stimulates embryonic development of the nervous system

Clotting Factors

proteins that stimulate the formation of a blood clot

Cytokines

peptides that are usually released by immune cells. Function by coordinating the body’s defense against infection. Most cytokines are paracrines but a few can travel great distances in the body.

Histamine

• common cytokine

• Secreted by mast cells and plays a major role in allergic reactions and inflammation

• makes the eyes water and nose run

What does histamine do in the inflammation response?

Increases blood flow to the affected areas and causes fluid to leak out of blood vessels and into the tissue, making affected areas swell and turn red.

Neurotransmitters

chemicals released into interstitial fluid by neurons

• released from axon terminals by neurons. Axon terminals are always close to their target cell. Movement to the target cell is by simple diffusion

• Target cells include: other neurons, muscle fibers, glandular cells

Synapse

junction between the neuron and the target cell (synaptic signaling)

Presynaptic Neuron

cell that releases the neurotransmitter

Postsynaptic Cell

the target cell

Acetylcholine

• example of a neurotransmitter

• triggers muscle contractions in skeletal muscle

Hormones

chemicals released by endocrine glands. Travels in the bloodstream to its target cell which may be some distance away

• target cells for hormones are specific

Insulin

• example of a hormone

• secreted by the pancreas and acts on target cells with specific receptors to stimulate energy metabolism (glucose uptake by cells)

Neurohormones

released by a special group of neurons known as neurosecretory cells. Diffuse into blood and affect target cells throughout the body

Vasopressin (Antidiuretic Hormone)

• example of a neurohormone

• secreted by specialized cells in the pituitary gland

• target cells located in the kidney

4 Characteristics that Impact Chemical Messenger Activity

1. ability to dissolve in plasma (mostly water)

2. ability to cross lipid bilayer in plasma membrane

3. Lipophilic Molecules: easily pass through a plasma membrane but don’t dissolve in plasma

4. Lipophobic Molecules: easily dissolvable in plasma but don’t cross plasma membrane

5 Classes of Chemical messengers based on structure

1. Amino Acid messengers

2. Amine messengers

3. Peptide/Protein messengers

4. Steroid messengers

5. Eicosanoid Messengers

Amino Acid messengers

synthesized by neurons and serve as neurotransmitters in the brain and spinal cord

• lipophobic and hydrophilic

• Glu, Asp, Gly, GABA

Amine messengers

derived from amino groups

• lipophobic and hydrophilic

• Catecholamines, serotonin, histamine

Catecholamines

a group of amine messengers which contain a catachol group (6 carbon ring). derived from tyrosine

• dopamine, norepinephrine, (neurotransmitters) and epinephrine (hormone)

Serotonin

amine messenger derived from tryptophan

• influences learning, happiness, and sleep

• lack is thought to play a role in depression

• released as a vesicle via exocytosis

Histamine

synthesized via histidine and is an amine messenger

• released as a vesicle via exocytosis

Peptide/Protein messengers

composed of 2-100 bonded amino acids.

• peptide refers to smaller groups of bonded amino acids

• lipophobic and hydrophilic

• produced at ribosomes on rough ER

Steroid messengers

• derived from cholesterol

• lipophilic and hydrophobic

• all function as hormones

• testosterone, estrogen, aldosterone

• all synthesized in smooth ER

Eicosanoid messengers

group of paracrines that are produced by most cells in the body

• derived from arachidonic acid (20 carbon fatty acid associated with plasma membrane phospholipids)

• hydrophobic and lipophilic

• can’t be stored for use

• thromboxanes and prostaglandins

How are paracrines and neurotransmitters transported?

• released from cells near the target cell

• reach target cell by simple diffusion

• quickly broken down in interstitial fluid and become inactive, stopping spread of their signaling

How are hormones transported?

transported in blood dissolved form or bound to carrier proteins

How are hydrophobic messengers transported?

often bound to carrier proteins, not very soluble in interstitial fluid/blood

• most carrier proteins are specific but a few are general to all molecules (albumin)

Half life

the amount of time it takes for half of the hormone in the blood to be degraded. Varies from one messenger to the next

4 Properties of Receptors

1. specific: usually only bind 1 messenger

2. interaction with messenger is brief and reversible

3. a single messenger can bind to multiple receptors

4. a single cell has multiple receptors and can respond to multiple different chemical messengers

3 Factors that influence magnitude of response

1. messenger concentration

2. number of receptors present in plasma membrane

3. affinity

Receptor Agonists

ligands that bind to receptors and induce a response

• morphine is an opioid agonist that binds to receptors in the brain and spinal cord; thus, blocking pain signals from reaching the brain

Receptor Antagonists

ligands that bind to receptors and block a response

• naloxone is an antagonist that attaches to morphine receptors and blocks the receptor so morphine can’t attach

Lipophilic Messengers

• freely and easily pass through the plasma membrane into the cytosol

• receptors are readily available

  • often bind to DNA to activate transcription. mRNA is produced and used to translate the production of a specific protein at ribosomes

Steroid Receptors also found in

cytoplasm and nucleus

Thyroid Receptors found in

nucleus

Lipophobic Messengers

• cannot permeate the plasma membrane

• receptors typically located on the plasma membrane and face the extracellular fluid

3 Types of Receptors for lipophobic messengers

1. Channel-linked receptors

2. enzyme-linked receptors

3. G-linked receptors

Channel-linked Receptors

chemical messenger binds to an ion channel which promotes opening of the channel

• mostly, channel produces effect by changing electrical properties of cell

• channels are typically specific

• most described as fast channels since response is immediate

• slow channels require a special protein (G protein) to link messenger to ion channel

Enzyme-lined receptors

• function as both enzymes and receptors

• receptor side faces tissue fluid

• enzyme portion faces cytosol

  • responds by catalyzing a reaction within the cell

• messenger causes conformational change of the receptor which triggers the enzyme to catalyze a reaction

Tyrosine Kinases

• most enzyme-linked receptors

• catalyze the addition of a phosphate group to the side chain of tyrosine

  • changes the activity which brings about a change in target cell

• typically very fast

  • ex: insulin

G-linked receptors

• work by activating specific membrane proteins (G Proteins)

  • named because they lead to the bonding of a phosphate group to Guanosine diphosphate (GDP) to produce Guanosine Triphosphate (GTP)

• GTP activates an effector molecule, reverse reaction returns the target cell to inactive state